The candidate applying for this award is an Assistant Professor of Pediatrics at Baylor College of Medicine (BCM). She has obtained a Master's of Science degree through the BCM Clinical Scientist Training Program and has published several first-author manuscripts in well-respected peer-reviewed pediatric journals. Her research focus is the hemodynamic status of extremely low birth weight (ELBW) infants. Extreme prematurity is an important public health problem in the U.S. because these infants are disproportionately affected by moderate to severe long-term disabilities, which are quite costly. There is little information, however, on the prevention of the short-term outcomes that result in disabilities in ELBW infants, most of which likely have their genesis from hemodynamic clinical deterioration during the first week of life. The overall objective of this proposed NHLBI Career Development Award application is to develop a series of multivariate clinical deterioration indices (CDIs) which will provide, in real-time, continuous and calibrated measurements of the likelihood of experiencing certain debilitating outcomes (and 1 clinical variable and 1 milestone) in ELBW infants and depict whether the responses to clinical interventions were successful. This will be accomplished through 3 specific aims, which are to: 1) Create independent CDIs from analysis of the physiologic inputs during the first week most associated with short-term outcomes (or the clinical variable/milestone) in ELBW infants; 2) Measure changes in each CDI prior to and after interventions used to treat hemodynamic clinical deterioration; and 3) Validate each CDI prospectively in a separate cohort of ELBW infants. In Aim 1, CDIs will be developed based on normalized logistic regression models. Separate models will be developed for each of 6 specific outcomes/clinical variable/milestone (intraventricular hemorrhage, periventricular leukomalacia, maternal creatinine clearance, necrotizing enterocolitis, intestinal perforation, and time to reach full feeds). For Aim 2, in the subset of this cohort who received interventions (e.g. fluid boluses or vasoactive medications), the CDI will be analyzed prior to and after each intervention to evaluate responses to treatment of perceived hemodynamic clinical deterioration. The final portion (Specific Aim 3) of the proposed research is validation of the CDIs in a separate cohort. Upon completion of the proposed research, the CDIs can be used in real-time to manage therapies with an evidence- and physiology-based approach never before available to clinicians or researchers. This will promote a shift from population-centric to individualized data- driven approaches, providing more effective care and surveillance for complex patients. The candidate will acquire important skills on her pathway to independence. Training activities during the award period include coursework and training in targeted neonatal echocardiography, training and practice in near-infrared spectroscopy and cerebral Doppler ultrasound, training in physiologic waveform analysis and predictive analytics, and training in the responsible conduct of research. Immediate career goals include becoming an expert in targeted neonatal echocardiography and proficient in the other monitoring modalities. The candidate is fortunate to have the facilities and resources available to her at BCM and Texas Children's Hospital (TCH). BCM had total research support of nearly $200 million from NIH in 2014 and is ranked # 1 in Texas for NIH funding. TCH is an internationally recognized 650-bed pediatric hospital affiliated with BCM. The mission of TCH, which is ranked nationally in all 10 pediatric subspecialties in the 2014-15 U.S. News & World Report, is to support excellence in patient care, education, and research with a commitment to enhance the health and well-being of children locally, nationally, and internationally. U.S. News & World Report ranked both the Neonatology Section and the Section of Pediatric Cardiology at TCH as #2 of U.S. programs in 2014-15. The candidate has assembled a scientific advisory committee with complementary intellect and content expertise that can guide her throughout the award period. The committee combines clinical insights from investigators in neonatology, pediatric cardiology, and pediatric anesthesiology with engineering and mathematical expertise in both physiologic signal processing and data analytics. The innovative approach in this proposal uses multiple monitoring methods, automated data capture, and real- time analysis to address a significant public health need for improving the knowledge base required to prevent common, costly, debilitating outcomes of ELBW infants. The proposed award is consistent with the NHLBI mission to promote the prevention and treatment of heart, lung, and blood diseases and enhance the health of all individuals so that they can live longer and more fulfilling lives. The exceptional resources and institutional support at BCM and TCH, outstanding multi-disciplinary mentorship team, and the proposed career development activities, will allow the candidate to achieve her long-term goal of becoming an independent investigator and nationally recognized expert in neonatal hemodynamics.